Faced with an inadequate supply of oxygen, the cell uses anaerobic glycolysis in an attempt to maintain the normal cell function, causing an accumulation of lactic acid and the release of hydrogen ions derived from ATP hydrolysis, causing a decrease in the pH of the tissue (see Bibliographic Reference (1)). Thus, the early changes in the pH of the tissue are useful for assessing the oxygenation of that tissue and the status of its microcirculation (2).
In the critically ill patient, when compensatory mechanisms fail to maintain a suitable oxygenation in all tissues, the neurohumoral response of the organism causes a redistribution of the blood flow aimed at preserving the function of “noble organs” such as the brain and the heart, at the expense of decreasing the infusion of “non-vital organs” such as the skin and splanchnic territory (3). Unlike the skin, the splanchnic territory, and particularly the intestinal mucosa, has high metabolic needs that along with certain anatomical characteristics that make it particularly susceptible to hypoxia, account for the intestine being the first organ to be affected in situations of hypoperfusion/hypoxia, and the last one to recover (2, 4). Therefore, the assessment of the tissue oxygenation at this level by monitoring the gastric intramucosal pH (pHi), will allow us to detect these situations early and prevent further worsening thereof, as well as to guarantee full recovery after an obvious shock episode (2, 4, 5).
The pHi can be measured by a microelectrode inserted in the gastric mucosa, but the invasiveness of the method, the impossibility of in vivo recalibration and frequent detachment of the electrode, make it impractical in the clinic (6). Therefore, we turn to the indirect measurement of pHi, based on the principle of tonometry, by which the gases diffuse freely through the tissues. Thus, in 1959 Boda and Murányi (7) made an estimate of the arterial PCO2 in more than 400 children mechanically ventilated for poliomyelitis, using a tonometry probe similar to the current ones, and inserted in the stomach through the nose. Their clinical experience led them to conclude that: 1) The arterial CO2 tension can be estimated with reasonable accuracy with the gastrotonometric method. 2) In patients in severe shock situation the PCO2 in the tonometer may be deceptively high. However, they do not understand the reason for this after fact. These results were subsequently confirmed by Bergofsky (8) by demonstrating that the fluid in the lumen of a hollow organ (urinary bladder, gallbladder, stomach), balances the tension of the gases (PO2 and PCO2) with that of the cells and tissues containing thereof, and these in turn with that of the blood irrigating thereof. And simultaneously also by Dawson (9) that observed in experimental animals how the PO2 and the PCO2 measured in the saline serum instilled in intestinal pouches experienced changes proportional to those of the blood. Therefore, the measurement of the CO2 Pressure in the gas in the lumen of the intestine is equivalent to the CO2 Pressure in the intestinal mucosa (10).
In 1982, Fiddian-Green et al (11) use these findings for postulating that the intestinal mucosa pH can be calculated in an indirect way. This hypothesis is based on two assumptions: 1) The PCO2 tonometrically measured approximates to that of the intestinal mucosa, since the CO2, for its high diffusion capacity, quickly reaches the balance between the tissue and the intraluminal lumen. 2) The bicarbonate concentration in the intestinal mucosa is in balance with that of the intestinal capillary bed, and this in turn, with that of the arterial blood (1). Therefore, the pHi calculation can be performed by a modification of the Henderson-Hasselbalch equation:pHi=6.1+log 10([HCO3−]/PgCO2*0.03)  Equation 1
Wherein 6.1 is the pK of the HCO3−/CO2 system in plasma at 37° C.; [HCO3−] is the arterial concentration of bicarbonate (mM/L); PgCO2 is the PCO2 of the tonometry probe set to the equilibrium time; 0.03 is the solubility constant of the CO2 in plasma at 37° C.
Thus, the deceptive PCO2 increases of the stomach in relation to the arterial PCO2, observed by Boda and Murányi in patients in situation of severe shock, would correspond to pHi drops as a result of regional tissue hypoperfusion. Grum et al, in 1984 develop a tonometry probe constituting the basis of the current commercial equipments. Using this equipment in dogs, they observed how the pHi remained constant as long as the blood flow was maintained above a critical value. Below this the pHi decreased. Moreover, these decreases in the pHi were accompanied by decreases in the O2 consumption. In 1990 Antonsson et al (6) validate the technique in an experimental model, by comparison of the tonometrically calculated pHi with that obtained from microelectrodes implanted directly in the mucosa of the stomach.
Classically, 2 other derived parameters have been used. To calculate them the arterial pH values (pHa) are used, obtained with the analysis of an arterial blood sample and the pHi, calculated by equation 1.Difference of pH or pHgap=pHa−pHi  Equation 2Standard intramucosal pH or pHis=7.4−pHgap  Equation 3
According to the place where the measurement of the CO2 in the lumen of the digestive tube (PgCO2) is performed, 2 types of measurement are distinguished:
1) Tonometry with CO2 analysis outside the organism: the technique consists of the placement of a nasogastric tube provided with a terminal silicone balloon permeable to CO2 that is left accommodated in the stomach. It is radio-opaque to facilitate its correct location by X-ray (Rx). It is therefore a minimally invasive technique. The analysis requires the extraction of the samples in order to be analysed. There are two types depending on the medium with which the balloon is filled:
A. Tonometry with physiological saline serum (PSS): it is the technique initially used and with which more experience is available. Thus, most of the studies that have evaluated its usefulness have been based on it. The technique requires, however, great user experience to obtain reliable results (12). The process of measuring can be divided in 2 times:                1. Measurement of the PgCO2: prior to the insertion of the catheter a careful purging of the balloon with PSS must be performed, to remove the air it may contain. After its insertion it is filled with 2.5 mL of the same serum, that is maintained over an equilibrium period (30 minutes minimum), that has to be known in case of being of less than 90 minutes, so that the correction is made. When extracting the sample the first mL must be discarded, corresponding to the dead space in the catheter, it must be preserved anaerobically (sealed) and processed immediately to be reliable. The measurement is performed in a standard blood gas analyzer, although there have been objectified important differences between different models, probably as a function of the calibration (it is performed for blood samples, not for PSS), so that each centre has to determine its reference values (2).        2. Calculation of the pHi and related parameters: in order to calculate an arterial blood extraction must be performed. With this sample the arterial pH and PCO2 measurements are obtained in a standard blood gas analyzer. Using these measurements the analyzer itself performs the calculation of the arterial bicarbonate (HCO3−) that along with the PgCO2 obtained from the tonometry probe allow the calculation of the pHi according to Equation 1. This calculation along with the measurement of the arterial pH, allow the calculation of the pHgap and pHis according to Equations 2 and 3.        A value of pHi<7.31 is generally considered abnormal (13). Therefore, the tonometry technique with saline serum is too cumbersome, requires user experience, is little reproducible and does not provide continuous information. For these reasons, although it has proved to be useful in research studies, it has not been introduced as a usual monitoring technique in critically ill patients. Currently, these probes are no longer marketed.        
B. Tonometry with air: to overcome some of the limitations of the tonometry with saline, the Datex-Ohmeda company adapted a capnograph (Tonocap®) that automatically filled the balloon with air, extracting the same periodically (every 10 minutes) to perform the measurements of the PgCO2. The technique was validated by several authors (14-16). Subsequently, an improvement in this equipment, the M-Tone Module of the same manufacturer (currently belonging to the General Electric group) was marketed. These equipments automate the measurements of the PgCO2, but for the calculation of the pHi it is still required to perform intermittent blood extractions that must be analyzed in a standard blood gas analyzer, and the results thereof entered manually in the apparatus. Therefore, although part of the measurement process has been automated, the technique continues to be intermittent and cumbersome.
To mitigate these disadvantages, the use as an indicator of tissue hypoperfusion of a related regional parameter has been proposed, the gastric-arterial CO2 gradient or CO2gap can be calculated as follows:CO2gap or P(g−a)CO2=PgCO2−PaCO2  Equation 4
Wherein PaCO2 is the CO2 arterial pressure. This parameter also requires the performing of intermittent blood extractions to obtain the PaCO2. Therefore, the PCO2gap is not measured continuously either. However, the manufacturer has incorporated in the equipment a second capnograph to measure continuously the CO2 end-expiratory pressure (EtCO2), as a way of approximation to the PaCO2, since in normal conditions the EtCO2 is related to the PaCO2 (the difference between both measurements in healthy volunteers is usually of 2 to 5 mmHg). Thus, it performs in an automated and continuous way, the calculation of a new derived parameter: the gradient between the gastric and expiratory CO2:CO2gap(et) or P(g−Et)CO2=PgCO2−EtCO2  Equation 5
However, the connection between the PaCO2 and the EtCO2 is lost frequently in the critically ill patient (target patient for the implementation of this monitoring). For this reason, the integration of these two parameters has not proven clinical usefulness and the device has fallen into disuse. Still, this equipment and its sampling probes are still marketed by the Datex-Ohmeda company and are available at an international level.
Moreover, the Datex Ohmeda S5 multiparametric system, with M-Tone tonometry module and capnograph for the measurement of the EtCO2, only provides a numerical value of the latest measurement. It does neither represent the data graphically nor does it show trends facilitating the interpretation of the data and assessing its evolution over time.
2) Tonometry with CO2 “in situ” analysis: the measurement of the CO2 in the lumen of the stomach (PgCO2) can be performed “in situ” and in real time by the placement of a fiber optic sensor. This sensor has been developed by The Institute of Chemical Process Development and Control. It has been applied in healthy volunteers and in intensive care patients. However, for this parameter to have clinical usefulness its integration with other systemic variables allowing the calculation of derived regional parameters is necessary. This device offers only this measurement, so it has little clinical usefulness.
As we have seen, the indirect calculation of the pHi or the CO2gap requires intermittent blood extractions to be obtained in order to obtain the bicarbonate or the PaCO2, along with the measurement of the PgCO2. The technique, therefore, is cumbersome and does not provide continuous information, which seriously limits its clinical use. Moreover, the attempt of integration for continuous measuring of the M-Tone Module has not resulted effective so far.
The system described herein overcomes the important limitations of the instruments currently in use, mainly the M-Tone Module of the Datex-Ohmeda company (currently belonging to the General Electric group). Additionally, the present system can estimate in a continuous and automated way the pulmonary physiological dead space in the critically ill patient.